Carbohydrates (Chapter 24) Flashcards
Empirical Formula of Carbohydrates
Cm(H2O)n
Monosaccharide
Simple Sugar
An aldehyde/ketone containing at least three carbon atoms and two hydroxyl groups.
A monosaccharide can be either an aldose OR a ketose.
Linkage Connecting Two Monosaccharides
Ether Linkage
Aldose vs. Ketonse
- Aldose: A monosaccharide containing an aldehyde group.
- Ketose: A monosaccharide containing a ketone group.
Nomenclature: Monosaccharide Chain Length
- Triose: 3 Carbons
- Tetraose: 4 Carbons
- Pentose: 5 Carbons
- Hexose: 6 Carbons
Numbering: Aldose vs. Ketose
- Aldose: Numbering begins at the aldehydic carbon.
- Ketose: Numbering begins at the terminal carbon closest to the ketone.
Monosaccharides: L-Enantiomers
The highest-numbered hydroxyl group substituent is located on the left side of the projection.
The highest-numbered carbon stereocenter has the S-conformation.
Monosaccharides: D-Enantiomers
The highest-numbered hydroxyl group substituent is located on the right side of the projection.
The highest-numbered carbon stereocenter has the R-conformation.
Five-Membered Cyclic Hemiacetal
Furanose
The five-membered furanose ring is more stable than the six-membered pyranose ring.
Six-Membered Cyclic Hemiacetal
Pyranose
The six-membered pyranose ring is more stable than the five-membered furanose ring.
Stereoselectivity of Pyranose
The pyranose stereoisomer that places the C1 hydroxyl group at the equitorial position (i.e. the R-isomer) will be the dominant product.
The placement of the C1 hydroxyl group at the equitorial position minimizes steric effects.
Stereochemsitry of Cyclic Hemiacetal Formation
Hemiacetal cyclization forms a pair of diasteromers (i.e. anomers) due to stereoisomerization at the aldehydic (C1) carbon.
The new stereocenter of hemiacetal cyclization is formed at the former aldehydic carbon.
Anomer
A stereoisomer of a cyclic hemiacetal
Mutarotation
The interconversion between the α-anomer and β-anomer of a cyclic hemiacetal.
The mutarotation interconversions occur while the aldoses are in the acyclic form. (The α-anomer and β-anomer of the cyclic aldose are in equilibrium in solution).
α-Anomer vs. β-Anomer
Cyclic Hemiacetals
- α-Anomer: The C1 hydroxyl group and highest-numbered hydroxyl group are placed on the same side of the cyclic projection.
- β-Anomer: The C1 hydroxyl group and highest-numbered hydroxyl group are placed on opposite sides of the cyclic projection.
The stereochemistry/configuration at the anomeric carbon is the ONLY difference between the α-anomer and β-anomer.
Anomeric Carbon
Cyclic Hemiacetals
C1 Carbon
The anomeric carbon is the hemiacetal carbon of a cyclic monosaccharide.
Stereoisomer Priority Trend
—OH > —COOH > —CH2OH
Acyclic Monosaccharide → Cyclic Hemiacetal
Hemiacetal Cyclization
The hemiacetal cyclization reaction can occur under basic conditions OR acidic conditions.
Cyclic Hemiacetal → Acyclic Monosaccharide
Cyclic Hemiacetal Ring-Opening
The hemiacetal cyclization reaction can is reversible.
Reagents: Hemiacetal Cyclization
- Acid-Catalyzed: H+, H2O
- Base-Catalyzed: OH–, H2O
The hemiacetal cyclization reaction CAN occur under neutral conditions (but the cyclization rate is much slower without a catalyst).
Enantiomer-Switching
D-Saccharide → L-Saccharide
All chiral centers within the aldose/ketose are inverted to the opposite stereoisomer configuration.
Fischer Projections: Monosaccharides
- Carbon atoms are numbered top-to-bottom.
- Horizontal bonds are depicted as wedges.
Determining Anomer Stereochemistry
- α-Anomer: The anomeric/hemiacetal carbon and the highest-numbered carbon have OPPOSITE stereoisomer configuration.
- β-Anomer: The anomeric/hemiacetal carbon and the highest-numbered carbon have the SAME stereoisomer configuration.
Mutarotation: Interconversion Explanation
Interconversion results from the varying plane-of-attack of the alcohol/oxide group to form the cyclic hemiacetal. (Attack of the alcohol/oxide group from above the molecule plane OR below the molecule plane creates differing anomeric forms of the cyclic monosaccharide.)
Both cyclic anomeric forms of the monosaccharide are in equilibrium with the acyclic aldose conformation.
Plane Analysis: Determining Anomer Stereochemistry
This plane analysis technique functions ONLY when the endocyclic Oxygen is bonded to the highest-numbered carbon.
- α-Anomer: The anomeric hydroxyl group and the terminal CH2OH group are on OPPOSITE planes of the cyclic configuration.
- β-Anomer: The anomeric hydroxyl group and the terminal CH2OH group are on the SAME plane of the cyclic configuration.
Strength of Aldose Oxidants
Bromine-Water < Nitric Acid < Periodic Acid
- Bromine-Water: Oxidation of Terminal Aldehyde ONLY.
- Nitric Acid: Oxidation of Terminal Aldehyde AND Terminal Alcohol.
- Periodic Acid: Oxidation of ALL Carbon-Carbon Bonds
Aldose → Aldonic Acid
Bromine-Water Oxidation
Weak Oxidation
The Bromine-Water Oxidation reaction converts the terminal aldehyde group to a carboxylic acid group.
Aldonic Acid
A sugar-acid monosaccharide containing one terminal carboxylic acid group.
Aldose → Aldaric Acid
Nitric Acid Oxidation
Medium Oxidation
The Nitric Acid Oxidation reaction converts the terminal aldehyde group AND terminal alcohol group to carboxylic acid groups.
Aldose → Carboxylic Acid + Aldehyde
Periodic Acid Oxidation
Strong Oxidation
The Periodic Acid Oxidation reaction oxidizes ALL carbon-carbon (C—C) bonds to C—OH or C=O bonds
Ketose → Caboxylic Acid + Aldehyde + CO2
Periodic Acid Oxidation
Strong Oxidation
The Periodic Acid Oxidation reaction oxidizes ALL carbon-carbon (C—C) bonds to C—OH or C=O bonds
Aldaric Acid
A sugar-acid monosaccharide containing two terminal carboxylic acid groups.
Reagents: Bromine-Water Oxidation
Br2, H2O
Reagents: Nitric Acid Oxidation
HNO3, H2O
Reagents: Periodic Acid Oxidation
HIO4 (Excess)
Product Identities: Periodic Acid Oxidation
- Ketones → CO2
- Aldehydes → Formic Acid
- 2° Alcohols → Formic Acid
- 1° Alcohols → Aldehydes
Formic Acid vs. Formaldehyde
- Formic Acid: 1-Carbon Carboxylic Acid
- Formaldehyde: 1-Carbon Aldehyde
Aldose → Alditol
NaBH4 Reduction
The NaBH4 Reduction reaction reduces the terminal aldehyde group to an alcohol group.
Ketose → Alditol
NaBH4 Reduction
The NaBH4 Reduction reaction reduces the ketone group to a 2° alcohol group.
Reagents: NaBH4 Reduction
NaBH4, CH3OH (Solvent)
Mild/Weak Oxidants
- Bromine-Water: Br2, H2O
- Silver: Ag(I)
- Copper: Cu(II)
Why are 2° alcohol groups NOT oxidized during Nitric Acid Oxidation?
The 2° alcohol groups are too sterically hindered to interact with the nitric acid oxidant.
Reaction: Sugar Chain Extension
Cyanohydrin Formation-Reduction
- The Cyanohydrin Formation-Reduction reaction creates two new sugars (due to formation of a stereocenter) that are one carbon longer than the starting aldose.
Reagents: Cyanohydrin Formation-Reduction
Starting Material: Aldose
- HCN
- H2, Pd
- H2O
Mechanism: Cyanohydrin Formation-Reduction
- HCN Attack at Aldehydic Carbon
- Hydrogenation across C≡N Bond
- Hydration of Imine Group
Pyranose → Multi-Pyranoside
Furanose → Multi-Furanoside
Base-Catalyzed William Ether Synthesis
The base-catalyzed William Ether Synthesis reaction converts ALL hydroxyl groups (on the pyranose) to methoxy groups.
Pyranose → Mono-Pyranoside
Furanose → Mono-Furanoside
Acid-Catalyzed Anomeric Hydroxyl Methylation
The acid-catalyzed Anomeric Hydroxyl Methylation reaction converts ONLY the anomeric hydroxyl group to a methoxy group (i.e. it converts the hemiacetal group to an acetal group).
Reagents: Base-Catalyzed William Ether Synthesis
Saccharide Acetal Formation
NaOH, (CH3)2SO4
Reagents: Acid-Catalyzed Anomeric Hydroxyl Methylation
Saccharide Acetal Formation
CH3OH, H3O+
Glycoside
Acetal-Containing Monosaccharide
Stability of Glycoside Acetals
- The acetal group is stable under basic conditions AND neutral conditions.
- The acetal group is cleaved under acidic conditions.
- Mutarotation of glycoside acetals does NOT occur under basic conditions or neutral conditions.
- Mutarotation of glycoside acetals DOES occur under acidic conditions (after the acetal is converted to a hemiacetal).
Reagents: Cleavage of Glycoside Acetal
H3O+, Δ (Heat)
Stability of Cyclic Acetals
Cyclic acetals are stable under basic conditions AND neutral conditions.
1,2-Diol → Cyclic Acetal
Ketone, H3O+
Methods of Sugar Hydoxyl Protection
- Cyclic Acetal Synthesis via 1,2-Diol
- Base-Catalyzed William Ether Synthesis
- Acid-Catalyzed Anomeric Hydroxyl Methylation
Disaccharide → Monosaccharide
Ether Linkage Cleavage
The α-anomer AND β-anomer of the monopyranose are formed. (The anomer with the anomeric hydroxyl group placed at the equitorial position will predominate.)
Reagents: Ether Linkage Cleavage
H3O+
Why are hemiacetal —OH groups more reactive than simple —OH groups under acidic conditions?
Pyranose Cleavage
Reaction of the hemiacetal —OH group with acid (i.e. protonation) results in a more stable oxocarbenium intermediate form.
Reaction of the simple —OH group with acid results in a less stable carbocation intermediate form.
